We propose to examine the corneal endothelial cells in vivo by two methods: 1) Using a modified clinical specular microscope and 2)Utilizing an entirely new concept in endothelial visualizaton with holography. The data obtained will be analyzed by conventional counting and two new methods, optical drum scanning densitometry and diffraction pattern sampling. The results obtained will be compared to those from the clinical specular microscope in current use to test the validity of this widely used system. In addition, we intend to provide the first documented clinico-pathological correlations between the in vivo appearance of normal and abnormal endothelial cell areas as viewed through the modified clinical specular microscope, with scanning electron microscopy of the same cells. A computer pattern recognition program and a Zeiss III epi-illuminator photomicroscope will be used in human in vivo experiments to localize particular endothelial areas while a laser marker modification to the clinical specular microscope will be used as an in vivo marker system in animal experiments. These experiments will introduce entirely new concepts in corneal endothelial assessment in vivo and will establish beyond doubt whether the interpretation of the data from currently available clinical specular microscope systems is indeed valid. In addition, we will, for the first time, standardize a method of endothelial examination. Finally, we will establish an accurate method of clinico-pathological correlation of normal and diseased endothelium.